Background

Accelerated partial breast irradiation (APBI) is defined as the delivery of large dose per fraction to the surgical cavity as part of a breast conservation approach (lumpectomy followed by radiation)

The smaller treatment volume of the surgical cavity plus margin (compared with standard whole breast irradiation) permits radiation to be given in a shorter period of time with larger dose per fraction.

A dose of 38.5 Gy in 10 fractions over 5 days (twice daily radiation) was delivered.

WBI technique was standard tangential fields with dose of 50 Gy in 25 fractions or 42.5 Gy in 16 fractions. Boost was optional.

The study was designed as a non-inferiority trial, with sample size adequate to detect an ipsilateral breast recurrence rate of 1.5% with WBI and 85% power to confirm that APBI is no worse by a margin of 1.5%.

A planned interim safety analysis was performed after a median follow-up of 2.5 years based on nurse-assessed adverse cosmesis.

The Data Safety Monitoring Commission recommended release of these results upon review.

A trial nurse and the patient assessed Cosmesis at baseline, 3 years, and 5 years following treatment.

Cosmesis was scored using the EORTC Cosmetic Rating System for Breast Cancer. Compared with the untreated breast, the treated breast was graded from 0 (no difference) to 3 (large difference) for size, shape, location of areola/nipple, telangiectasia, and scar.

Trial nurses were trained with a detailed guide and set of training slides.

This plenary session is reporting only on the global cosmetic result.

The grading was independently validated by two panels of 3 radiation oncologists each, all trained with a detailed guide and slides and all blinded to the treatment provided to the patient.

Consensus method was used to administer a score, and inter-panel reliability was high with Kappa 0.71.

Results

The arms of the study were well-balanced with respect to baseline and treatment characteristics.

1065 women were enrolled on the WBI arm, and 1070 on the APBI arm.

The majority of women were age ³ 50 years, with invasive disease, tumor size £ 1.5 cm, and ER-positive. 83% of women had 42.5Gy in 16 fractions and boost was used in only 21%.

Nurse assessment of adverse cosmetic outcome showed adverse cosmesis at baseline was 18% in both arms. At 3 years, adverse cosmesis in the APBI had deteriorated to 32%, while the WBI arm remained at 19%. The difference in cosmesis at 3 years was statistically significant.

Blinded physician panel assessment detected a similar and statistically significant difference in cosmesis between the arms.

335 patients had 5 years of follow-up, and the inferior cosmesis seen with ABPI continued at 5 years.

Patient self-evaluation of cosmesis shows the same effect of ABPI-produced inferior cosmetic outcomes, but the difference in cosmesis between ABPI and WBI was of lesser magnitude.

Analysis of late radiation toxicity at 3 years, showed an increase in grade 1 and 2 toxicity in APBI compared with WBI, primarily from breast induration and telangiectasia.

Author's conclusions

In this interim analysis, APBI was associated with adverse cosmetic outcome at 3 and 5 years.

APBI also had increase in grade 1 and 2 toxicity. Grade 3 toxicity was very uncommon in both arms.

The observed increase in toxicity may have resulted from infrequent use of boost in the WBI arm, limited conformality in the APBI arm, lack of adequate repair time, or the asymmetric nature of partial breast irradiation.

Further research is necessary to determine if there is a group of patients who can be treated with APBI with limited toxicity.

Implications

The authors correctly highlight that studies are mixed with regards to the cosmetic effects of APBI with some showing acceptable cosmesis, and others showing high rates of poor cosmesis.

The strength of this study is the methodology for cosmesis assessment. The study is unique in that cosmesis was assessed at baseline and over time by trial nurses, patients, and an independent panel of physicians blinded to the treatment received.

Another strength is the randomized study design and the high inter-rater reliability.

The early cosmesis results are compelling, and demonstrate the APBI using a 3D-CRT technique may provide significantly worse cosmesis than standard fractionated whole breast external beam radiation.

These results may or may not be applicable to other methods of APBI, such as interstitial or balloon-based techniques. These techniques typically irradiate a lower volume of breast tissue compared with external beam, 3D-CRT APBI.

Another issue may be related to the WBI arm, in which very few patients received boost radiation. This may have led to more favorable cosmesis ratings in that arm that would otherwise be observed if a boost were used.

The APBI technique has grown rapidly in acceptance, and is currently being used nationwide for patients deemed to be acceptable candidates based on cooperative group guidelines.

This study highlights that complete and long-term toxicity and cosmetic data are not yet fully available, and caution should be exercised in using these techniques in patients off-protocol.

We await a detailed analysis of toxicity and cosmetic outcomes from the RAPID study, as well as analysis of long-term control rates.

In the future, further study of dose/fractionation and highly conformal partial breast techniques may yield an approach which can compress the radiation treatment schedule without sacrificing local control outcomes or exacerbating long-term toxicity or cosmesis.